The impact of opiate abuse on cell-mediated immunity (CMI) needs better definition because CMI is both a major defense against virus infection and also the primary target of HIV. Prior studies either predate the HIV epidemic and do not use modern immunologic study population. To rectify this gap in our knowledge, we will survey immune competence in a group of opiate-dependent patients as they progress from unregulated heroin use to controlled methadone use to a drug-free state. We theorize that chronic opiate exposure will inhibit various parameters of CMI, and that these effects may differ between unregulated "street" abuse and controlled use of methadone. Moreover, our survey will gather important information regarding the safety of chronic methadone administration. One hundred HIV antibody-negative, heroin-dependent patients will be studied acutely, and after 1, 4, 12, and 24 weeks of methadone maintenance. In addition, the estimated 15% who electively transfer to drug-free status will be studied again immediately before and one month after withdrawal from methadone. Patients and matched control subjects will have the following tests of cell-mediated immune function: 1. Lymphocyte transformation in response to mitogens and antigens. The assays will be conducted in the presence and absence of opiate in the test system. 2. Extensive lymphocyte phenotyping by flow cytometry. 3. Natural killer cell activity against normal target cells and those infected with HIV. Assays will be done in 10% autologous or control serum to look for possible inhibitors. 4. The competence of monocyte/T-cell interaction will be assessed by measuring the ability of circulating monocytes to elaborate the lymphokine IL-1 when stimulated. 5. Delayed hypersensitivity will be measured in vivo to a battery of antigens. Finally, patients will be given a battery of psychological tests to define their degrees of psychopathology. These results will be correlated with the progressive state of the subjects' CMI, utilizing multivariate analysis.